Cancer continues to be one of the foremost health problems. Conventional treatments such as surgery and chemotherapy have been extremely successful in certain cases; in other instances, much less so. Radiation therapy has also exhibited favorable results in many cases, while failing to be completely satisfactory and effective in all instances. An alternative form of radiation therapy, known as microbeam radiation therapy (MBRS) or microbeam radiosurgery (MBRS) may be used to treat certain tumors for which the conventional methods have been ineffective.
MBRS differs from conventional radiation therapy by employing multiple parallel fan beams of radiation with a narrow dimension or thickness that may be on the order of 10 micrometers to 200 micrometers. The thickness of the microbeams is dependent upon the capacity of tissue surrounding a beam path to support the recovery of the tissue injured by the beam. It has been found that certain types of cells, notably endothelial cells lining blood vessels, but also oligodendroglial and other supporting cells, have the capacity to migrate over microscopic distances, infiltrating tissue damaged by radiation and reducing tissue necrosis in the beam path. In MBRS, sufficient unirradiated or minimally irradiated microscopic zones remain in the normal tissue, through which the microbeams pass, to allow efficient repair of irradiation-damaged tissue. As a result, MBRS is fundamentally different from other forms of radiation therapy.
In conventional forms of radiation therapy, including the radiosurgical techniques employing multiple convergent beams of gamma radiation, each beam is at least five hundred micrometers wide, so that the biological advantage of rapid repair by migrating or proliferating endothelial cells is minimal or nonexistent. Observations of the regeneration of blood vessels following MBRS indicate that endothelial cells cannot efficiently regenerate damaged blood vessels over distances on the order of more than 100 micrometers (μm). Thus, in view of this knowledge concerning radiation pathology of normal blood vessels, the skilled artisan may select a microbeam thickness as small as 20 μm but not more than 100 μm. Further, the microbeams may include substantially parallel, non-overlapping, planar beams with center-to-center spacing of from about 50 μm to about 500 μm. Also, the beam energies may range from about 30 to several hundred keV. These microbeams result in a dosage profile with peaks and valleys. The radiation dosage in the peaks is large enough to kill the targeted tumor, but also kills healthy cells in the peak dosage areas. The region between the peaks is called the valley region. The minimum radiation dosage in the valleys (i.e., the “nadir” valley dosage) is small enough to prevent clonogenically lethal damage to all potentially reparative cells in the valley dosage areas.
A division of a radiation beam into microbeams and the use of a patient exposure plan that provides non-overlapping beams in the tissue surrounding the target tumor allows the non-target tissue to recover from the radiation injury by migration of regenerating endothelial and other reparative cells of the small blood vessels to the areas in which the endothelial cells have been injured beyond recovery. Therefore, the probability of radiation-induced coagulative necrosis in normal, non-targeted tissue is lowered, which may improve the effectiveness of clinical radiation therapy for deep-seated and/or superficially situated tumors.
Various studies have shown the microbeam tissue-sparing effect for X-ray microbeams. Although other methods and processes are known for radiation therapy, none provides a method for performing radiation therapy while avoiding significant radiation-induced damage to tissues proximal to, distal to, and interspersed with the targeted lesion.
Present radiation therapies often take many days and weeks of treatment to provide enough radiation to a target tumor. On the other hand, MBRS can provide an effectual treatment in a single visit. Very high-energy radiation may be used with MBRS that results in the destruction of tumor tissue while allowing for the regeneration of healthy tissue affected by the microbeams.
Further, MBRS provides a method for treating cancerous tumors by using extremely narrow, quasi-parallel X-ray microbeams increasing the precision and accuracy of radiation therapy. MBRS also provides a method of using extremely small microbeams of radiation to unexpectedly produce effective radiation therapy while avoiding significant radiation-induced damage to non-targeted tissues.
A major benefit of MBRS is that the microbeams are so narrow that the vasculature of the tissue and other components of the tissue through which the microbeams pass can repair themselves by the infiltration of endothelial cells and other cells from surrounding unirradiated tissue. Present knowledge indicates that such infiltration can take place only over distances on the order of less than 500 μm and depends on the specific tissue being irradiated. The dimensions of the microbeams and the configuration of the microbeam array are therefore determinable with reference to the susceptibility to irradiation of the target tissue and the surrounding tissue to irradiation and the capacities of the various involved tissues to regenerate.
In MBRS it is possible to define an extraordinarily narrow penumbra (edge between the peak and valley regions) between the area radiated and the adjacent very low radiation area. Once the microbeams enter tissue they may be scattered and/or absorbed. The photoelectric effect and Compton scattering dominate the two interactions of the initial microbeam with the tissue. Both of these effects are photon-energy-dependent and the scattering angle distribution is well characterized in the physics literature. In both of these interactions electrons are emitted and may potentially go in any direction and may travel distances comparable to the width of the area irradiated by the microbeam. Some of these electrons will stay within the boundaries of the width of the irradiated area, which corresponds to a desired treatment area, while others will exit this area, and hence potentially damage untreated tissue. The electrons that exit the exact area of the initial microbeam treatment area and deposit their energy effectively act to blur the sharp line between the intensely irradiated area (peak) and the area of minimal radiation (valley). Widening of the penumbra (blurring at the edge between the peak and valley regions) is detrimental to the desired dose delivery and can: harm the adjacent healthy tissues; limit useful microbeam treatment depth; limit depths of tumors below the skin; limit the types of tumor/lesions/conditions treated; and limit the usefulness of MBRS in general.
Confining the radiation dose and/or damage geometry of the scattered electrons to the intended Microbeam treatment area (peaks) and out of the spared regions (valley) between the Microbeam peaks would enhance the efficacy of the radiation therapy. In some cases the spread of the radiation dose and/or damage region outside of the intended peak area would limit or prevent the usefulness of Microbeam treatment because of the detrimental effect of the radiation dose and/or damage in the unplanned valley regions.
U.S. Pat. No. 5,339,247 to Slatkin et al. titled Method for Microbeam Radiation Therapy provides additional background related to MBRS, and is hereby incorporated by reference for all purposes as if fully set forth herein.